The long-term goal of this laboratory is to gain an understanding of the chemical basis of nociception in the primate. The focus of this project is to determine the chemical basis of excitation of the spino-reticular (SRT), the spino-mesencephalic (SMT) and the spino-hypothalamic tracts (SHT) in response to afferent stimulation. There is compelling evidence that these pathways, in addition to the spinothalamic tract (STT), provide the main channels for the rostral transmission of nociceptive information. Although the functions of the STT seems established, a clear understanding of the functions of the other three pathways remains elusive. As a first step to define better the role of these other tracts, it is necessary to understand the manner in which these pathways are activated by primary afferent stimuli and to determine the plasticity in the responses of these tracts after peripheral injury. Earlier studies have shown that two classes of primary afferent transmitters, the excitatory amino acids peripheral stimulation under normal conditions. In addition, earlier studies have shown that plasticity of dorsal horn neurons following peripheral injury, evidenced most frequently by an increase, or sensitization, of responses to peripheral stimuli, also mediated by an affect of excitatory amino acids and neurokinin peptides. The proposal outlined here is composed of three aims to test the global hypothesis that a similar chemistry underlies the activation of the three major afferent pathways in the anterolateral spinal cord listed above. Specifically, we propose to determine the following concerning the SRT, SMT and SHT: the role of excitatory amino acid and neurokinin receptors in the activation of these pathways in normal conditions; whether the responses of these pathways show an enhancement of function (sensitization) following peripheral injury or inflammation, or following injury to a spinal nerve; and the role of excitatory amino acid and neurokinin agonists in the sensitization of these pathways.